Neoadjuvant Chemotherapy or Chemoradiotherapy Outperform Surgery for Esophageal/GEJ Carcinoma

Matthieu Faron, MD, Institut de Cancérologie Gustave Roussy, Villejuif, France, discusses findings from an individual participant data network meta-analysis which identified the best neoadjuvant treatment for patients with esophageal or gastroesophageal junction (GEJ) carcinoma across prespecified subgroups.

These findings were presented at the 2022 ESMO World Congress on Gastrointestinal Cancer in Barcelona, Spain.

Transcript:

Hello everyone. I'm Dr. Matthieu Faron. I'm a surgical oncologist and biostatistician from Gustave Roussy, France. This morning, I presented the result of the MANATEC-02 study, which is a study on the best new adjuvant treatment for carcinoma of the esophagus.

For carcinoma of the esophagus or the gastroesophageal junction, when tumors are locally advanced, we already know that chemotherapy followed by surgery is better than surgery alone. We also know that chemoradiotherapy followed by surgery is better than surgery alone. But little is known on the direct comparison of chemoradiotherapy to chemotherapy. Moreover, carcinoma of the esophagus is a heterogeneous disease with several histologies like squamous cell carcinoma and adenocarcinoma, and different tumor locations. Whether the best new adjuvant treatment is the same in all tumor locations is still unknown.

We designed a network meta analysis based on individual patient data with Cox 1-step mixed effect model. Trials were selected by searching databases online, like PubMed, by conference proceeding and by trial register like clinicaltrial.gov. Our main end point was the overall survival. Trials were included if they were randomized and closed to enroll before 2015. All histologies on tumor location were accepted. We only excluded patients with unavailable individual patient data.

At the end, we were able to retrieve 26 trials representing more than 4900 patients. The most performed comparison was chemotherapy, followed by surgery versus surgery in 14 trials, then chemoradiotherapy followed by surgery versus surgery in 12 trials. Finally, the most interesting comparison, chemoradiotherapy versus chemotherapy, was only performed in 4 studies. Fortunately, the network meta analysis will allow to combine direct and indirect evidences to better estimate this comparison.

Our patients were 60 years of age, were mostly male, with good performance status. Histologies were somewhat well-balanced between squamous cell carcinoma and adenocarcinoma. Most of the tumors were located in the thoracic esophagus. In the direct comparison, which is like 3 separate meta analyses, we confirmed that chemotherapy followed by surgery is better than surgery, and chemoradiotherapy followed by surgery also better than surgery, but we found no significant differences in the comparison of chemoradiotherapy versus chemotherapy.

In the network meta analysis, combining all the direct and indirect evidence, we had a lot of power with more than 3000 events of death, some heterogeneity, but not inconsistency. Our main finding was that the comparison of chemoradiotherapy to chemotherapy showed no significant difference, with the hazard ratio equal to 0.9. We confirmed that chemotherapy was better than surgery, and chemoradiotherapy also better than surgery.

Finally, in the subgroup analysis, one of the surprises was to see that treatment performed equally in all histological subtypes, so the notion that chemoradiotherapy was more effective for squamous cell carcinoma was not confirmed. On the other end, we observed that the tumor location was a treatment effect modifier for nearly all comparisons, with a greater treatment effect for tumor located at the gastroesophageal junction, greater than that of the thoracic esophagus. The novel treatment effect modifier was sex, which was significant for the chemoradiotherapy followed by surgery versus surgery alone comparison, with a greater treatment effect for female patients.

In conclusion, we confirmed that chemotherapy followed by surgery was greater than surgery. Chemoradio followed by surgery was also greater than surgery, with no variation with the histological subtypes. Some variation with the gender, some variation of the tumor location. And for the most interesting comparison, chemoradiotherapy followed by surgery versus chemotherapy followed by surgery, despite the large power of this network meta analysis we found no significant differences. Thank you for your attention.

Source:

Faron M, Cheugoua-Zanetsie M, Thirion P, et al. Individual participant data network meta-analysis (IPD-NMA) of neoadjuvant chemotherapy or chemoradiotherapy in esophageal or gastro-esophageal junction carcinoma. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract SO-4.